Articular cartilage lines the ends of articulating bones in diarthroidal joints of the body. It is composed of collagen fibrils, a proteoglycan matrix and chondrocytes (the cells that produce cartilage matrix). Mature articular cartilage has a limited capacity for regeneration after degeneration or injury. Lesions within mature articular cartilage are generated during the course of many joint diseases, notably osteoartritis (OA), traumatic damage and osteochondritis dissecans (Hunziker, 2002). Traumatic lesions may occur directly or indirectly in consequence of an intraarticular fracture, a high-intensity impact or following ligament injuries (Buckwalter et al., 1998). Articular cartilage lesions generally do not heal, or heal only partially under certain biological conditions. They are frequently associated with disability and with symptoms such as joint pain, locking phenomena and reduced or disturbed function. Moreover, such lesions are generally believed to progress to severe forms of OA (Gilbert, 1998; Hunziker, 2002).
The numerous experimental and clinical attempts that have been made to induce the healing of histologic and macroscopic lesions within mature articular cartilage aim at re-establishing a structurally and functionally competent repair tissue of an enduring nature.
There are two major biological problems associated with articular cartilage repair. The first problem is the construction of repair tissue with the same structural and mechanical properties as articular cartilage (Shapiro et al., 1993). The second problem is to achieve successful integration across the interface between the host and repair tissue.
An important prerequisite for long-term repair or regeneration of articular cartilage is the integration of transplanted cartilage or locally induced repair tissue with the native cartilage at the recipient site (Ahsan et al., 1999; Hunziker, 1999). Integrative cartilage repair is probably hindered by the lack of matrix-producing cells in the cartilage-cartilage interface area (Ahsan et al., 1999; Reindel et al., 1995). The acellularity is due to a combination of chondrocyte loss from lesion edges, avascularity, or the absence of multipotent progenitor cells.
Current methods used in the clinic to encourage natural cartilage repair include debridement, subchondral drilling or microfracture and mosiacoplasty. Such techniques usually results in fibrocartilagenous repair tissue that fails mechanically with time. More importantly, there is no way to monitor the quality of the repair tissue generated.
Autologous chondrocyte implantation (ACI) is the first generation of cell based therapy of articular cartilage defects. It is based on expanding autologous articular chondrocytes taken from non-weight bearing area and implanting them into a defect under a periosteal or collagen flap (Gillogly, 2003). The object is to keep the implanted cells in place until they can form cartilage.
The second generation of cartilage tissue engineering involves using biodegradable scaffolds seeded with expanded chondrocytes to create a an immature, implantable construct that can fill the defect.
However, ACI and immature constructs can only be used to treat confined defects. These procedures are not suitable for treatment of the unconfined lesions that are typical of osteoarthritis, a degenerative joint disease involving the loss of articular cartilage. For better treatment of unconfined lesions it is desirable to have a “sheet” of ready-formed mature cartilage to resurface the entire lesion. Accordingly, there is an interest in engineering mature cartilage tissue in vitro in order to produce mature, functionally- and mechanically-sound implants ready to fill cartilage defects such as those caused by osteoarthritis.
Once positioned over the lesion, it is necessary that the engineered mature cartilage integrates with the existing cartilage surrounding the lesion to form a unified tissue which provides a durable articular surface. Integration of the repair tissue with surrounding native cartilage is a critical step in the development of cartilage tissue engineering strategies. Initial, temporary fixation of an engineered cartilage implant may be achieved using sutures or fibrin glue. However there will be a clear discontinuity between the implant and host cartilage, creating a focus for failure (Hunziker, 1999). There is no clear evidence in the literature demonstrating that integration of adjacent surfaces in vivo occurs either readily or consistently. This can be explained by the poor environment of the defect characterised by collagen fibrillation and fissure formation (Donohue et al., 1983; Thompson et al., 1991). Furthermore, blunt trauma was shown to cause apoptosis of chondrocytes of the defect walls (Redman et al., 2004).